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- Wang, HD, et al.
(author)
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Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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In: Lancet (London, England). - : Elsevier. - 1474-547X .- 0140-6736. ; 388:10053, s. 1725-1774
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Journal article (peer-reviewed)
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- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Granrud, MD, et al.
(author)
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Health Care Personnel's Perspectives on Quality of Palliative Care During the COVID-19 Pandemic : A Cross-Sectional Study
- 2023
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In: Journal of Multidisciplinary Healthcare. - : Dove Medical Press. - 1178-2390. ; 16, s. 2893-2903
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Journal article (peer-reviewed)abstract
- Purpose: The provision of high-quality palliative care is challenging, especially during a pandemic like COVID-19. The latter entailed major consequences for health care systems and health care personnel (HCP) in both specialist and community health care services, in Norway and worldwide. The aim of this study was to explore how the HCP perceived the quality of palliative care in nursing homes, medical care units, and intensive care units during the COVID-19 pandemic. Methods: This study had a cross-sectional design. A total of 290 HCP from Norway participated in the study (RR = 25.8%) between October and December 2021. The questionnaire comprised items concerning respondents' demographics and quality of care, the latter measured by the short form of the Quality from the Patient's Perspective-Palliative Care instrument, adapted for HCP. The STROBE checklist was used. Results: This study shows that the HCP scored subjective importance as higher in all dimensions, items and single items than their perception of the actual care received. This could indicate a need for improvement in all areas. Information about medication, opportunity to participate in decisions about medical and nursing care and continuity regarding receiving help from the same physician and nurse are examples of areas for improvement. Conclusion: Study results indicate that HCP from nursing homes, medical care units, and intensive care units perceived that quality of palliative care provided was not in line with what they perceived to be important for the patient. This indicate that it was challenging to provide high-quality palliative care during the COVID-19 pandemic.
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- Larsson, AK, et al.
(author)
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Relationship between maternal and child cytokine responses to allergen and phytohaemagglutinin 2 years after delivery
- 2006
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In: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 144:3, s. 401-408
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Journal article (peer-reviewed)abstract
- Little is known at present about the relation between parental and child cytokine profiles. In this study we aimed to investigate the cytokine profile of 2-year-old children and their corresponding mothers, 2 years after delivery. Peripheral blood mononuclear cells (PBMC) were isolated from IgE-sensitized (n = 15) and non-sensitized (n = 58) 2-year-old children and their mothers. The responses to ovalbumin, cat and phytohaemagglutinin (PHA) were investigated using the enzyme-linked immunospot (ELISpot) technique. Interferon (IFN)-γ-, interleukin (IL)-4-, IL-10- and IL-12-producing cells were enumerated. At 2 years of age, IgE-sensitized children exhibited increased numbers of IL-4-producing cells in response to PHA and also showed an increase in IL-10- and IL-12-producing cells to allergen that was more pronounced in response to ovalbumin than to cat. A statistically significant increase in the numbers of IFN-γ-, IL-10- and IL-12-producing cells to the allergens, but not to PHA, was found in the mothers of IgE-sensitized children irrespective of their own atopic status. IgE levels and cytokine responses were correlated between the mothers and their children, indicating that cytokine responses to both allergen and PHA might be governed by genetic factors. We speculate that the increased cytokine response to allergen, as opposed to the allergic status of the mother, might be a better predictor and/or a risk factor for the child to develop IgE-sensitization in early life.
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